VIDEO: Exposure to High-Fat Diet In Utero Reprograms Liver, Leads to Metabolic Disease

In utero exposure to a high-fat diet reprograms the liver, leads to long-term gene dysregulation, and ultimately to metabolic disease, according to the results of an animal study recently published in Endocrinology.

Researchers led by Maureen J. Charron, PhD, of Albert Einstein College of Medicine in the Bronx, N.Y., point out that it’s already known that in utero exposure to a high-fat diet is associated with increased incidence of cardiovascular disease, diabetes, and metabolic syndrome later in life. But why that is, isn’t particularly well understood. “Although models of fetal programming of metabolic disease have described changes in DNA methylation,” the authors write, “evidence supporting this hypothesis remains limited. Thus, using our established model of in utero programmed metabolic syndrome, we sought to determine whether genome-wide changes in DNA methylation occur in liver of offspring exposed to a maternal HF diet.”

In their analysis, the researchers found 3,360 differentially methylated loci, “most of which (76%) were hypermethylated and distributed preferentially to hotspots on chromosomes 4 [atherosclerosis susceptibility quantitative trait loci (QTLs) 1] and 18 (insulin-dependent susceptibility QTLs 21),” they write. From those hotspots, the researchers found six differentially methylated genes that are associated with metabolic disease and remain altered through adulthood. “Most of the hypermethylated genes in these hotspots are associated with cardiovascular system development and function,” the authors write.

Charron and her team conclude that these results support the hypothesis that maternal high-fat diet causes changes in the liver and DNA that carry over into adulthood and cause metabolic disease. Still, they write, future studies are needed to include characterization of DNA methylation in different hepatic cell types.

Check out a video of Charron discussing her team’s findings below.

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